Inclusion Criteria:

1. ≥ 18-year-old males or females
2. Histologically or cytologically confirmed metastatic colorectal cancer or other gastrointestinal malignancy for which FOLFOX6 chemotherapy is a standard treatment. Other gastrointestinal cancers include, but are not limited to, esophageal, gastric, and small intestine, appendiceal, and pancreatico-biliary cancers.
3. Documented progressive disease
4. Measurable or evaluable disease by RECIST. (Note: Subjects enrolled in the MTD Expansion Cohort are required to have measurable disease, according to RECIST.)
5. No more than 2 prior chemotherapy regimens for metastatic disease (This does not include prior adjuvant chemotherapy with fluorouracil and/or oxaliplatin.)

6. At least 3 weeks since prior treatment with:

   • Chemotherapy (at least 6 weeks for nitrosoureas, mitomycin C, and liposomal doxorubicin)
   • Agents targeting the VEGF pathway (eg, bevacizumab, sunitinib, sorafenib, etc.)
   • Other signal transduction inhibitors and monoclonal antibodies
   • Immunotherapy or biological response modifiers
   • Systemic hormonal anti-cancer therapy, with the exception of LHRH agonists for prostate cancer
   • Any experimental therapy
7. Resolution of toxicities associated with prior chemotherapy to ≤ Grade 1 (except for Grade 2 alopecia)
8. ECOG performance status ≤ 2 (see Appendix A) and life expectancy ≥ 3 months
9. No childbearing potential or use of effective contraception by all fertile male and female subjects during the study and for 30 days after the last dose of study drug. All subjects must agree to use a highly effective method of contraception (including their partner). Effective birth control includes (a) IUD plus one barrier method; or (b) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm). Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study.
10. Dated and signed informed consent

Exclusion Criteria:

1. Primary CNS malignancies or clinically active CNS metastases
2. Hematologic malignancies (includes leukemia in any form, lymphoma, and multiple myeloma)

3. Any of the following hematologic abnormalities:

   • Hemoglobin < 9.0 g/dL
   • ANC < 1500 per mm3
   • Platelet count < 100,000 per mm3

4. Any of the following serum chemistry abnormalities:

   • Total bilirubin > 1.5 × ULN
   • AST or ALT > 2.5 × ULN (or > 5 x ULN for subjects with liver metastasis)
   • GGT > 2.5 x ULN (or > 5 x ULN for subjects with liver metastasis)
   • Alkaline Phosphatase > 2.5 x ULN (or > 5 x ULN for subjects with liver or bone metastasis)
   • Serum albumin < 3.0 g/dL
   • Creatinine > 1.5 × ULN (or calculated CLCR <50 mL/min/1.73 m2)
   • Proteinuria > 2.5 g/24 hours or 3+ with urine dipstick
   • Any other ≥ Grade 3 laboratory abnormality at baseline (other than those listed above)

5. Significant cardiovascular disease, including:

   • Active clinically symptomatic left ventricular failure
   • Active HTN (diastolic blood pressure > 100 mmHg). Subjects with a history of hypertension must have been on stable doses of anti-hypertensive drugs for ≥ 4 weeks prior to start of Cycle 1
   • Uncontrolled hypertension: Blood pressure >140/90 mmHg on more than 2 antihypertensive medications
   • Myocardial infarction within 3 months prior to start of Cycle 1
6. Serious/active infection, or infection requiring parenteral antibiotics
7. Inadequate recovery from any prior surgical procedure or major surgical procedure within 6 weeks prior to the start of Cycle 1
8. Unhealed wounds, ulcers, or bone fractures
9. Ongoing hemoptysis or history of clinically significant bleeding
10. Cerebrovascular accident within 12 months prior to the start of Cycle 1, or peripheral vascular disease with claudication on walking less than 1 block
11. Deep venous thrombosis or pulmonary embolus within 12 months prior to the start of Cycle 1 and/or ongoing need for full-dose oral or parenteral anticoagulation
12. History of ≥ Grade 3 hypersensitivity reaction with prior exposure to oxaliplatin
13. Subjects with a "currently active" second malignancy other than non-melanoma skin cancers or localized prostate cancer (with stable PSA for at least 3 months prior to the start of Cycle 1). Subjects are not considered to have a "currently active" malignancy if they have completed anti-cancer therapy and are considered by their physician to be a < 30% risk of relapse.
14. Life-threatening illness or organ system dysfunction compromising safety evaluation
15. Uncontrolled psychiatric disorder or altered mental status precluding informed consent or necessary testing
16. Inability to comply with protocol requirements
17. Pregnant or lactating women
18. Known concomitant genetic or acquired immune suppression disease, such as HIV
19. Consumption of herbal preparations/supplements (except for a daily multivitamin/mineral supplement not containing herbal components) within 2 weeks prior to the start of Cycle 1

20. Prior radiotherapy:

    • Local radiation therapy (involving ≤ 25% of bone marrow) within 2 weeks prior to the start of Cycle
    • Craniospinal radiotherapy within 3 months prior to the start of Cycle 1
    • Radiotherapy to: whole abdomen or pelvis, whole lungs, > 25% of bone marrow, or total body irradiation within 6 months prior to the start of Cycle 1