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Inclusion Criteria:

* Patients must have pathologically confirmed adenocarcinoma of the colon or rectum.
* In patients with liver-limited metastatic colorectal cancer, a curative approach is indicated following evaluation by hepatobiliary surgeon as part of multidisciplinary management. Select patients requiring two stage procedure are also eligible following evaluation by hepatobiliary surgeon as part of multidisciplinary management.
* In patients with rectal cancer, primary tumor that is clinically T3-4 or N + (evaluation by colorectal surgery is required as part of multidisciplinary approach).
* No prior chemotherapy for metastatic disease is allowed for patients with CRC-liver mets. (adjuvant FOLFOX is permitted)
* No prior chemotherapy for proximal rectal cancer is allowed
* ECOG Performance status ≤ 2.
* Age \>18 years old.
* Patients must have adequate bone marrow, kidney, and liver function as assessed by laboratory parameters.

  1. WBC ≥ 3,000/uL
  2. Total Bilirubin ≤ 1.5 x upper limits of normal
  3. AST (SGOT) ≤ 3 x upper limits of normal
  4. ALT (SGPT) ≤ 3 x upper limits of normal
  5. Hemoglobin ≥ 9.0 g/dl (without transfusion within 7 d)
  6. ANC ≥ 1500 /ml
  7. Platelets ≥100 K/ml (without transfusion)
  8. Calculated CrCL \> 50 ml/min
* Ability to understand and the willingness to sign a written informed consent document.
* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.

Exclusion Criteria:

* Patients with untreated CNS metastases.
* Significant medical co-morbidity that would preclude safe administration of cytotoxic therapy, including but not limited to:

  1. Cardiovascular disease

     1. Unstable angina
     2. Myocardial infarction/ CABG \< 3 months prior to study initiation
     3. Untreated coronary artery disease
     4. NYHA class III or IV heart failure
  2. Ongoing serious infection

     1. Bacteremia or sepsis requiring intravenous antibiotics
     2. HIV with AIDS defining illness
  3. Inadequate oral nutritional intake: Requirement for daily intravenous fluids or total parenteral nutrition.
  4. Neurological: Stroke ≤ 6 months
  5. Psychiatric illness/social situations that would limit compliance with study requirement
* Patients may not receive another investigational agent.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to Ziv-aflibercept.
* Pregnant (positive pregnancy test) and lactating women are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.
* Major surgical procedure ≤ 4 weeks from starting therapy.
* Grade 3-4 hemorrhage, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, or diverticulits ≤ 3 months from starting therapy.
* Patients with known DPD deficiency
* Patients with known Gilbert's syndrome
* Patients with ≥ 2g/24 hour urine protein. If urine protein on random UA is ≤ 300 mg/dl, a 24 hour urine protein is not required.
* Symptomatic peripheral sensory neuropathy grade ≥ 2.
* Other malignancy within the last 5 years from study entry, except for basal /squamous cell skin cancer, in situ cervical cancer, or non-metastatic prostate cancer.

• New York, New York, United States