Irinotecan Plus Brivanib in Metastatic Colorectal Cancer (CRC) Enriched for Elevated Levels of Plasma FGF

Inclusion Criteria:

1. Signed written Informed Consent.
2. Patient must have progressed on front-line chemotherapy treatment containing bevacizumab for histologically confirmed colorectal adenocarcinoma that is unresectable or metastatic. Progression is defined as either radiographic or clinical progression.
3. Patient must have measurable lesions as defined by RECIST version 1.1 criteria.
4. ECOG performance status 0-2.
5. Known bFGF level performed by a CLIA-certified laboratory performed during or within 12 weeks of last bevacizumab treatment
6. Enrollment in the "Assessment of Targeted Therapies Against Colorectal Cancer" (ATTACC) protocol 2009-0091.
7. LVEF \> 50% measured by 2-D echocardiogram
8. Bone marrow function defined as the following: An absolute neutrophil count (ANC) =/\>1,500/mcl; Platelets =/\>100,000/mcl; Hemoglobin =/\> 8.5 g/dl.
9. Renal function defined as the following: Serum creatinine less than or equal to 1.5 x institutional upper limit normal (ULN).
10. Hepatic function defined as the following: Serum total bilirubin \< 1.5 x ULN; AST (SGOT), ALT (SGPT) and alkaline phosphatase =/\< 2.5 x ULN; Serum albumin =/\> 2.5 g/dl; If liver involvement, AST, ALT, and alkaline phosphatase =/\< 5.0 x ULN.
11. International normalized ratio (INR) =/\< 2.3 or Prothrombin Time (PT) =/\< 6 seconds above control unless patient is currently receiving warfarin therapy for the treatment or prevention of venous thrombosis.
12. Men and women, age =/\> 18 years.
13. A male subject of fathering potential must use an adequate method of contraception to avoid conception throughout the study \[and for up to 12 weeks after the last dose of study drug\] to minimize the risk of pregnancy. If the partner is pregnant or breastfeeding, the subject must use a condom.
14. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of study drug to minimize the risk of pregnancy. WOCBP must have a negative serum or urine pregnancy test within 72 hours before the start of the investigational product.

Exclusion Criteria:

1. Women who are pregnant or breastfeeding.
2. Patients with brain metastases.
3. Patients with resectable colorectal cancer or non-adenocarcinoma cancer of the colon or rectum.
4. Patients who have had prior therapy with brivanib, anti-PDGFR (platelet-derived growth factor receptor) or anti-FGFR (fibroblast growth factor receptor) therapy.
5. Recent (within 4 weeks of the first study drug administration), or planned participation in another experimental therapeutic drug study.
6. Recent (within 4 weeks of the first study drug administration) infusion of bevacizumab therapy.
7. Prior irinotecan chemotherapy.
8. Prior full field radiotherapy =/\<4 weeks or limited field radiotherapy =/\<2 weeks prior to first study drug administration.
9. Recent use (within 4 weeks of first study drug administration) of St. John's Wort.
10. Patients with a history of thrombotic or embolic events within the last six months such as a cerebrovascular accident (including transient ischemic attacks), pulmonary embolism.
11. Patients with gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE (version 4.0) Grade 4 within 30 days prior to first study drug administration
12. Patients with uncontrolled or significant cardiovascular disease including: i) Active coronary artery disease, unstable or newly diagnosed angina or myocardial infarction \< 12 months prior to first study drug administration. ii) Class III-IV New York Heart Association (NYHA) congestive heart failure. iii) Uncontrolled hypertension (Systolic blood pressure \[BP\] \> 150 mmHg and diastolic BP \> 90 mmHg for 24 hours) despite optimal medical management. Blood pressure must be below 140/90 mmHg at screening. Subjects with a history of hypertension who are receiving treatment with calcium channel blockers that are CYP3A4 substrates should be changed to an alternative antihypertensive medication prior to first study drug administration. iv) Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin. v) QTc (Fridericia) prolongation \>450 msec. vi) Subjects with valvular heart disease =/\> CTCAE (Ver. 4.0) Gr 2. vii) Left ventricular ejection fraction (LVEF) \< 50%.
13. Active infection, less than 7 days after completing systemic antibiotic therapy.
14. History of non-healing wounds or ulcers, or bone fractures within 3 months prior to first study drug administration.
15. Major surgical procedure, open biopsy, or significant traumatic injury less than 3 weeks or those who receive minor surgical procedures (e.g. core biopsy or fine needle aspiration) within 1 week from first dose of first study drug administration.
16. Inability to swallow tablets or untreated malabsorption syndrome.
17. Pre-existing thyroid abnormality with thyroid function that can not be maintained in the normal range with medication.
18. History of human immunodeficiency virus (HIV).
19. Patients with centrally cavitating lung lesions.
20. Known bleeding diathesis.
21. Inability to comply with study and/or follow-up procedures.
22. Patients with known glomerular nephritis.
23. Patients with known polycythemia.
24. Patients with known Gilbert's syndrome.
25. Women with a positive pregnancy test.
26. Patients with hyponatremia (sodium \< 130 mmol/L).
27. Baseline serum potassium \< 3.5 mmol/L (potassium supplementation may be given to restore the serum potassium above this level prior to study entry).
28. Baseline serum calcium \< 8.4 mg/dL (calcium supplementation may be given to restore the serum calcium above this level prior to study entry).
29. Baseline serum magnesium \< 1.5 mg/dL (magnesium supplementation may be given to restore the serum magnesium above this level prior to study entry).
30. Known or suspected history of allergy to brivanib or any agents given in association with this study.
31. Prisoners or subjects who are involuntarily incarcerated. Patients who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.