Study to Identify Biomarkers of Clinical Response to Aflibercept in Patients With Metastatic Colorectal Cancer

Inclusion Criteria: 1. Histologically or cytologically proven adenocarcinoma of the colon or rectum, with at least one liver metastasis site available for biopsy. 2. Patients must have received only one prior chemotherapeutic regimen for metastatic disease. This prior chemotherapy must be an oxaliplatin containing regimen (in combination with bevacizumab). Patients who did not receive bevacizumab in their first-line treatment regimen may also be considered. 3. Metastatic disease that is not amenable to potentially curative treatment. 4. Measurable metastatic disease and evaluable disease. 5. ECOG 0 or 1. 6. Normal coagulation profile (PT, PTT, INR). 7. Provide written consent after the investigational nature, study design, risks and benefits of the study have been explained. 8. Age ≥ 18 years. Exclusion Criteria: 1. More than 1 prior chemotherapy regimen for metastatic colorectal cancer. Previous adjuvant FOLFOX based chemotherapy is allowed. 2. Relapse from adjuvant treatment within 6 month of completion of adjuvant chemotherapy. 3. Less than 42 days elapsed from prior major surgery to the time of registration. 4. Inadequate or unusable tissue as the only tissue available for biopsy. 5. Any of the following within 3 months of registration: Grade 3-4 gastrointestinal bleeding/hemorrhage, diverticulitis, pulmonary embolism, inflammatory or infections bowel disease, treatment resistant peptic ulcer disease, colitis, erosive esophagitis or gastritis, uncontrolled thromboembolic event. 6. Prior intolerance to bevacizumab due to toxicity. 7. Known dihydropyrimidine dehydrogenase (DPD) deficiency. 8. Gilbert's Syndrome. 9. Occurrence of deep vein thrombosis within 4 weeks, prior to registration. 10. Any of the following within 6 months prior to registration; myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, NYHA class III or IV congestive heart failure, stroke or transient ischemic attack. 11. Contraindication to any of the components of the FOLFIRI chemotherapy regimen, as per investigators' judgement. 12. Inadequate bone marrow function as follows: * Absolute neutrophil count (ANC) \< 1.5x 109/L * Platelet count \< 100 x 109/L * Hemoglobin \< 90 g/L 13. Inadequate liver function test: * Total bilirubin \> 1.5 x ULN * Transaminases \> 3 x ULN (if liver metastasis are present, 5 x ULN) * Alkaline phosphatase \> 3 x ULN (if liver metastases are present, 5 x ULN) 14. Contraindication to aflibercept. Including: * Urine protein-creatinine ratio (UPCR) \> 1 on morning spot urinalysis or proteinuria \>500 mg/24-h * Serum creatinine \> 1.5 x upper limit of normal (ULN). If creatinine 1.0 - 1.5 x ULN, creatinine clearance, calculated according to Cockroft-Gault formula, \< 60 ml/min will exclude the patient. * History of uncontrolled hypertension, defined as blood pressure \> 150/100 mgHG (grade ≥ 2 according to NCIC CTCAE v. 4.0), or systolic blood pressure \> 180 mmHG when diastolic blood pressure \< 90 mmHG, on at least 2 repeated determinations on separate days within 3 months prior to study enrollment. * Patients on anticoagulant therapy with unstable dose of warfarin and/or having an out-or-therapeutic range INR (\>3) within the 4 weeks prior to study entry. * Evidence of clinically significant bleeding diathesis or underlying coagulopathy (eg. INR\>1.5 without vitamin K antagonist therapy), non-healing wound. 15. Known active brain metastases or meningeal disease. 16. Female patients who are pregnant or breastfeeding. 17. Patients of reproductive potential (male and female) who do not agree to use an accepted form of contraception during the study period and up to 6 months following completion of study treatment. 18. Concurrent treatment with other anti-cancer therapy (palliative radiation is allowed but patients must have a metastatic site available for biopsy that has not been irradiated). 19. Known infection with HIV.