Study of Hydroxychloroquine With FOLFIRI and Bevacizumab in DTP-high Metastatic Colorectal Cancer

Inclusion Criteria: * Histologically confirmed colorectal cancer, not amenable to curative resection. * Microsatellite stable/mismatch repair proficient (MSS/pMMR) colorectal cancer. * No prior systemic therapy for metastatic disease. * Evaluable disease based on RECIST 1.1 criteria. * Adequate hematological, hepatic and renal functions * Eastern Cooperative Oncology Group (ECOG) Performance status 0-1. * Estimated life expectancy of \> 6 months. * Negative pregnancy test for female patients with child-bearing potential. * No history of retinal disorder. * No history of glucose-6-phosphate dehydrogenase deficiency (G6PD) . * Considered to be DTP-signature high to receive HCQ treatment Exclusion Criteria: * Women who are pregnant or nursing. * Have received radiotherapy, chemotherapy, biological therapy, or investigational treatment less than four weeks (six weeks for nitrosoureas or mitomycin C) prior to first dose of FOLFIRI-beva or have not recovered from all acute toxicities from prior treatments to grade 1 or less, with the exception of alopecia and those deemed not to affect safety assessment. * Have concurrent malignancy with exception of malignancy that was treated curatively and without evidence of recurrence within 3 years of study enrollment, or fully resected basal or squamous cell skin cancer and any carcinoma in situ which are considered to be of low risk of recurrence. * Have had major surgery within 28 days of study enrollment. Placement of a venous access device within 28 days of starting therapy is allowed. * Have any medical condition that would impair the administration of oral agents including significant bowel resection, inflammatory bowel disease or uncontrolled nausea or vomiting. * Known central nervous system metastasis. Patients with history of central nervous system metastases are eligible if they are clinically and radiographically stable for at least 3 months and not taking steroids or anticonvulsants.