A Study of FOLFIRI Plus OMP-21M18 as 1st or 2nd-line Treatment in Subjects With Metastatic Colorectal Cancer

Inclusion criteria 1. Subjects must have histologically confirmed metastatic colorectal cancer. Subjects may not have received more than 1 prior chemotherapy regimen for their metastatic disease and may not have received irinotecan for treatment of their metastatic disease. 2. Age \>21 years 3. ECOG performance status \<2 (see Appendix B) 4. Life expectancy of more than 3 months 5. Subjects must have normal organ and marrow function as defined below: * Leukocytes \>3.5 x 109/L * Absolute neutrophil count \>1.25 x 109/L * Hemoglobin \>100 g/L * Platelets \>125 X 109/L * Total bilirubin \<2 X institutional upper limit of normal (ULN) * Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) \<5 X institutional ULN * Alkaline phosphatase \<5 X institutional ULN * International normalized ratio (INR) and activated partial thromboplastin time (aPTT) within institutional ULN * Creatinine \<1.5 X institutional ULN OR * Calculated creatinine clearance \>60 mL/min using the Cockcroft and Gault formula as follows: Creatinine clearance (mL/min) = (140 - age) x ideal body weight \[kg\] 0.814 x serum creatinine \[µmol/L\] For women multiply the value from the equation above by 0.85. Where age is in years, weight is in kg, and serum creatinine is in µmol/L 6. Women of childbearing potential must have had a prior hysterectomy or have a negative serum pregnancy test and be using adequate contraception prior to study entry and must agree to use adequate contraception from study entry through at least 6 months after discontinuation of study drug. Men must also agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and from study entry through at least 6 months after discontinuation of study drug. Should a woman enrolled in the study or a female partner of a man enrolled in the study become pregnant or suspect she is pregnant while participating in this study or within 6 months after discontinuation of study drug, the Investigator should be informed immediately. 7. Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria Subjects who meet any of the following criteria will not be eligible for participation in the study: 1. Subjects receiving any other investigational agents or anti-cancer therapy. 2. Subjects with brain metastases (subjects must have a CT scan or MRI of the head within 28 days prior to enrollment to rule out brain metastases), uncontrolled seizure disorder, or active neurologic disease 3. History of a significant allergic reaction attributed to humanized or human monoclonal antibody therapy 4. Significant intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements 5. Pregnant women or nursing women 6. Subjects with known HIV infection 7. Known bleeding disorder or coagulopathy 8. Subjects receiving heparin, warfarin, or other similar anticoagulants. Note: Subjects may be receiving low-dose aspirin and/or non-steroidal anti-inflammatory agents. 9. Subjects with known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease 10. New York Heart Association Classification II, III, or IV (See Appendix D) 11. Subjects with a blood pressure of \>140/90 mmHg. The BP should be taken using the method described in Section 9.3. Subjects taking antihypertensive medications must be taking ≤ 2 medications to obtain this level of BP control. 12. Subjects with tumors that are currently involving the lumen of the gastrointestinal tract 13. Subjects with current evidence of cardiac ischemia or heart failure within the last 6 months, subjects who are receiving any medications for cardiac ischemia, subjects with a B-type natriuretic peptide (BNP) value of \>200 pg/mL, subjects with a LVEF \< 45%, or subjects that have received a total cumulative dose of ≥400 mg/m2 doxorubicin. 14. Subjects with ECG evidence of ischemia or ≥ Grade 2 ventricular arrhythmia, subjects who have a history of acute myocardial infarction within 6 months, or subjects with unstable angina.