Inclusion Criteria:

• Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum
• Stage IV or recurrent disease
• Measurable disease
• Disease progression or recurrence during or after completion of prior first-line chemotherapy with fluorouracil and leucovorin calcium (5-FU/LV)
• Prior irinotecan or oxaliplatin as part of the 5-FU/LV regimen or as subsequent therapy allowed
• Only 2 prior regimens for metastatic disease allowed
• One additional regimen as adjuvant therapy allowed provided patient remained disease-free for > 6 months after completion of therapy*
• Newer, targeted investigational agents (e.g., cetuximab or bevacizumab) are not

counted as a chemotherapeutic regimen unless used in combination with a cytotoxic regimen NOTE: *If evidence of failure occurred within < 6 months after completion of adjuvant therapy, patients may have received only 1 additional regimen for metastatic disease

• No active brain metastases (requiring treatment or progressing)

Exclusion Criteria:

• History of blood transfusion within 14 days
• Need of concurrent Administration of allopurinol
• History of Radiotherapy or Chemotherapy within 4 weeks
• Any psychological or sociological condition, addidtive disorder or family problems that might preclude compliance with the protocol
• Any unstable or severe intercurrent medical condition that in the opinion of th einvestigator might interfere with achievement of study objectives
• Receipt of an investigational agent within 28 days prior to first day of dosing with AG-2037
• Pregnant or breast feeding
• Previous treatment with GARFT inhibitors
• History of a malignancy (other than colorectal cancer) excpet those treated with curative intent for skin cancer (other than melanoma) or in situ breast or cervical cancer or those treated with curative intent for any other cancer with no evidence of disease for 5 years
• Active brain metastases (requiring treatment or progression)