Abstract: Colorectal cancer is one of the most common malignant tumors, and the main treatment for patients with advanced-stage disease is systemic drug therapy. The combination of FOLFOX or FOLFIRI with anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR) monoclonal antibodies has become the standard first-line treatment for advanced colorectal cancer. Fluorouracil, oxaliplatin, and irinotecan are three major chemotherapy drugs for colorectal cancer, and FOLFOXIRI, a combination of these three drugs, has been playing an important role in the treatment of advanced colorectal cancer in recent years. FOLFOXIRI has significantly improved the prognosis of patients with advanced colorectal cancer, but it is also associated with a significant increase in adverse effects. The concomitant reduction of adverse effects and maintenance of acurative effect represent important goals. This paper reviews the progress of research on the FOLFOXIRI regimen as first-line therapy for advanced colorectal cancer.