Inclusion Criteria:

• STEP 1: INITIAL REGISTRATION
  • The distal extent of the tumor must be ≥ 12 cm from the anal verge on endoscopy; if this distance was not confirmed on endoscopy pre-operatively, then the distal extent of the tumor must be ≥ 12 cm from the anal verge as determined by surgical examination; colonoscopy should be performed postoperatively for those unable to have a preoperative colonoscopy to guarantee there are no synchronous lesions; (if tumor is located beyond sigmoid colon and centimeter distance unavailable, include anatomic region of colon, e.g. right colon, transverse colon, hepatic flexure descending colon, cecum etc.)
  • Patients must have paraffin-embedded tumor specimen available for evaluation of microsatellite instability and loss of heterozygosity at 18q, to determine high risk versus low risk
    • High-risk patients will be randomized to treatment Arms A or B
    • Low-risk patients will be registered to Arm C for observation
      • NOTE: Every effort should be made to submit blocks (tumor and normal mucosa) to the Principal Coordinates Analysis (PCO) immediately; blocks CANNOT be accepted after day 50 (post surgery) in order to allow for molecular assessment
      • Specific laboratory requirements for Step 2 must be obtained within 2 weeks prior to Step 2 randomization
  • Patients must not have synchronous tumors
  • Patients must not have appendiceal tumors
  • Patients must not have a history of inflammatory bowel disease (IBD)
  • Patients with hereditary non-polyposis colorectal cancer (HNPCC) are eligible
  • Patients must have no history of isolated, distant, or non-contiguous intra-abdominal metastases, even if restricted
  • Patients must have histologically confirmed adenocarcinoma of the colon that meets the criteria below:
    • Stage II adenocarcinoma (pT3/pT4a/pT4b pN0 M0 according to the definitions of the American Joint Committee on Cancer, 7th Edition, 2010): the tumor invades through the muscularis propria into pericolic tissues (pT3), penetrates to the surface of the visceral peritoneum (pT4a), or directly invades other organs or structures (pT4b); patients with mesenteric tumor deposits or satellites without identifiable residual lymph node in the absence of lymph node involvement are now designated pN1c, rather than pT3; patients with such tumor deposits are not eligible for E5202; patients must have had a complete resection (R0 resection)
  • Patients must have ≥ 8 lymph nodes evaluated and reported
  • Patients must not have presented with clinical complete obstruction or perforation of the bowel
  • Patients must not have had any systemic or radiation therapy initiated for this malignancy
  • Patients must not have a previous or concurrent malignancy; exceptions are made for patients who meet any of the following conditions:
    • Non-melanoma skin cancer, in situ cervical cancer, or breast cancer in situ
    • Prior malignancy completely excised or removed and patient has been continuously disease free for > 5 years
    • Patients with completely excised or removed breast cancer and disease free > 5 years, regardless of the continuation of hormonal therapy
    • Patients with previous radiation therapy (RT) to the pelvic region will be ineligible
  • Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• STEP 2: RANDOMIZATION (HIGH RISK PATIENTS - ARMS A AND B ONLY)
  • Within 2 weeks prior to randomization, postoperative absolute granulocyte count (AGC) must be ≥ 1500/mm^3 (or < 1500/mm^3, if in the opinion of the investigator, this represents an ethnic or racial variation of normal)
  • Within 2 weeks prior to randomization, the postoperative platelet count must be ≥ 100,000/mm^3
  • Within 2 weeks prior to randomization, there must be postoperative evidence of adequate hepatic function; bilirubin must be ≤ upper limit of normal (ULN) unless the patient has a chronic grade 1 bilirubin elevation due to Gilbert's disease or similar syndrome due to slow conjugation of bilirubin
  • Within 2 weeks prior to randomization, there must be postoperative evidence of adequate hepatic function; alkaline phosphatase must be < 2.5 x ULN
  • Within 2 weeks prior to randomization, there must be postoperative evidence of adequate hepatic function; aspartate transaminase (AST) must be < 1.5 x ULN
  • Within 2 weeks prior to randomization, there must be postoperative evidence of adequate renal function; serum creatinine ≤ 1.5 x ULN
  • Within 2 weeks prior to randomization, there must be postoperative evidence of adequate renal function; urine protein/creatinine (UPC) ratio of < 1.0; patients with a UPC ratio ≥ 1.0 must undergo a 24-hour urine collection, which must be an adequate collection and must demonstrate < 1 gm of protein in order to participate
  • Patients with any significant bleeding that is not related to the primary colon tumor within 6 months prior to study entry are not eligible
  • Patients with gastroduodenal ulcer(s) determined to be active by endoscopy are not eligible
  • Patients with a history of hypertension must measure < 150/90 mmHg and be on a stable regimen of anti-hypertensive therapy
  • Patients must not have a serious or non-healing wound, skin ulcers or bone fracture
  • Patients experiencing clinically significant peripheral neuropathy at the time of step 2 randomization (defined in the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events version 4.0 [CTCAE 4.0] as grade 2 or greater neurosensory or neuromotor toxicity) are not eligible
  • Patients must not have had invasive procedures, defined as follows:
    • Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization
    • Core biopsy or other minor procedure, excluding placement of a vascular access device, within 7 days prior to randomization
    • Or anticipate the need for major surgical procedure(s) during the course of the study
  • Patients must begin adjuvant treatment no less than 28 days and no more than 60 days from surgery
  • Eligible patients of reproductive potential (both sexes) must agree to use an accepted and effective method of contraceptive during study therapy and for at least 3 months after the completion of bevacizumab; women must not be pregnant or breast-feeding; all females of childbearing potential must have a serum pregnancy test to rule out pregnancy within 2 weeks prior to step 2 randomization
  • Patients with prothrombin time (PT) (international normalized ratio [INR]) > 1.5 are not eligible, unless the patient is on full-dose anticoagulants; if so, the following criteria must be met for enrollment:
    • The subject must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin or on a stable dose of low molecular weight heparin
    • The subject must not have active bleeding or a pathological condition that is associated with a high risk of bleeding
  • Patients with non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude any of the study therapy drugs are not eligible; specifically excluded are the following conditions:
    • New York Heart Association (NYHA) class III or IV congestive heart failure
    • Current symptomatic arrhythmia
    • Any non-malignant systemic disease
  • Patients with a history of transient ischemic attack (TIA) or cerebrovascular accident (CVA) are not eligible
  • Patients with a history of the following within twelve months of study entry are not eligible:
    • Arterial thromboembolic events
    • Unstable angina
    • Myocardial infarction
  • Patients with symptomatic peripheral vascular disease are not eligible
  • Patients with psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude them from meeting the study requirements are not eligible
  • Patients must not have a known allergy to platinum compounds
• STEP 2: REGISTRATION (LOW-RISK PATIENTS - ARM C)
  • Patients determined to be low risk are eligible