The purpose of this Phase II study will be to investigate the antiangiogenic agent, aflibercept, in combination with chemoradiation as preoperative treatment for patients with stage II/III rectal cancer, followed by 4 months of FOLFOX6 plus aflibercept adjuvantly.

Inclusion Criteria:

1. Patients with histologically confirmed stage II or III rectal cancer (adenocarcinoma)
2. Patients must be candidates for preoperative chemoradiation
3. Male or female patients ≥18 years-of-age
4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1
5. Adequate hematologic, liver and renal function
6. Male patients willing to use adequate contraceptive measures
7. Female patients who are not of child-bearing potential, and female patients of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum or urine pregnancy test <7 days prior to start of treatment
8. Life expectancy ≥12 weeks
9. Willingness and ability to comply with the trial and follow-up procedures
10. Ability to understand the nature of this trial and give written informed consent.

Exclusion Criteria:

1. Treatment with prior chemotherapy or radiation for rectal cancer.
2. Patients who have received any other investigational agents within the 28 days prior to Day 1 of the study.
3. Known to be human immunodeficiency virus positive or hepatitis B or C positive
4. Women who are pregnant or breastfeeding
5. History of acute myocardial infarction within the previous 6 months, uncontrolled hypertension (blood pressure >150/100 mmHg and/or diastolic blood pressure >100 mmHg), unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication (excluding atrial fibrillation), or ≥ Grade 2 peripheral vascular disease.
6. History of hypertensive crisis or hypertensive encephalopathy.
7. History of stroke or transient ischemic attack within the past 6 months.
8. Significant vascular disease (eg, aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to initiation of therapy.
9. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months.
10. Patients with symptomatic sensory or peripheral neuropathy (Grade 2 or above).
11. Patients may not have received other agents, either investigational or marketed, that act by primary anti-angiogenic mechanisms.
12. Prior malignancy (except for adequately treated basal-cell or squamous-cell skin cancers, in situ carcinomas, or low grade [Gleason score of 3+3 or less] localized prostate cancer) in the past 5 years.
13. Patients with active concurrent infections or patients with serious underlying medical conditions.
14. Patients receiving full-dose oral or parenteral/SC anticoagulation must be on a stable dosing schedule prior to enrollment; a coumadin dose must be stable for 1 week. If this cannot be achieved, the patient will be ineligible for enrollment.
15. Major surgical procedure or significant traumatic injury within 28 days prior to study initiation, or anticipation of need for major surgical procedure during the course of the study.
16. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to initiation of therapy.
17. Patients with proteinuria, as demonstrated by a urine protein of 2+ or greater at screening. If 2+ or greater proteinuria, a 24-hour urine can be obtained, and if the result is <1 gm/24 hours, the patient is eligible.
18. Any non-healing wound, ulcer, or bone fracture.
19. Any clinical evidence or history of a bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
20. History of hemoptysis (≥½ teaspoon of bright red blood per episode) within 1 month prior to initiation of therapy.
21. History of any other disease, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the