Introduction In Cuba, colorectal cancer (CRC) is the malignant neoplasm with the fourth-highest incidence and third-highest mortality. Over one-third of CRC patients exhibit metastatic disease at the time of diagnosis. Standard treatment for metastatic CRC is a 5-fluorouracil (5-FU) + Folinic Acid (FA) continuous infusion regimen. International studies have shown, however, that systemic therapy using oxaliplatin combined with 5-FU and FA (FOLFOX-4) improves results in terms of both tumor response and survival in patients with inoperable metastatic CRC. Objective Evaluate the FOLFOX-4 regimen as a first-line therapy for patients with inoperable metastatic CRC in Cuba. Methods FOLFOX-4 therapy was administered to 56 patients with metastatic CRC, in a treatment cycle repeated every 2 weeks for 6-8 cycles. Patients were followed up for a period of 2 years. Results Objective response was attained in 44.6% of patients, and complete response in 12.5%. Median duration of response and of progression-free survival was 9.6 and 8.9 months, respectively. Estimated survival at 2 years was 17% (95% CI: 6.89-26.8). The most frequent adverse events were nausea, vomiting, diarrhea and neutropenia, the majority grade 1-2, according to Common Terminology Criteria for Adverse Events (CTCAE) classification. Conclusions In patients studied, the FOLFOX-4 combination was shown to be an effective and well-tolerated therapeutic option for treating inoperable metastatic colorectal cancer.