FOLFOX/Bevacizumab/Hydroxychloroquine (HCQ) in Colorectal Cancer

Inclusion Criteria:

* Patients must have histologically documented advanced or metastatic adenocarcinoma of the colon or rectum.
* Patients must have measurable disease as defined by the RECIST criteria as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as 20 mm with conventionaltechniques on either CT of MRI. Marker (CEA) elevation alone is insufficient for entry.
* Patients may have had prior adjuvant treatment of advanced colorectal cancer. The prior treatment regimen must not have included bevacizumab but may have included oxaliplatin and the last dose of chemotherapy must have been 6 months prior to study entry. Patients with prior radiotherapy are acceptable. It must be at least 2 weeks since administration of radiation therapy and all signs of toxicty must have abated.
* Patients must be 18 years or older.
* Patients must have an ECOG performance status of 0-1.
* The following required Initial Laboratory Values should be obtained within 4 weeks of the start of treatment: Granulocytes 1,500/ml, Platelet Count 100,000/ml, Creatinine 1.5 x upper limit of normal, Bilirubin 1.5 x upper limit of normal, AST 5 x upper limit of normal Urine Urine protein:creatinine ratio 1.0 at screening
* Patients must not be pregnant or lactating as chemotherapy is thought to present substantial risk to the fetus/infant.
* Patients must have a life expectancy of greater than three months.
* Patients must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* Major sugical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study. Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 0.
* Patients with serious nonhealing wounds, ulcers, or bone fractures.
* Patients with a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to Day 0
* Patients with a history of myocardial infarction, unstable angina, or cerebrovascular accident 6 months prior to registration.
* Patients with clinically significant peripheral vascular disease.
* Patients with New York Heart Association Class II or greater congestive heart failure (class II is defined as symptoms of fatigue, dyspnea or other symptoms with ordinary physical activity).
* Patients using oral or parenteral anticoagulation are not excluded provided they are on a stable dose of anticoagulant.
* Patients with pre-existing hypertension should be on a stable antihypertensive regimen and have a blood pressure 150/100 mmHg at the time of enrollement.
* Patients must not have known brain metastases because the study drug has not been adequately tested in this setting.