Colorectal cancer(CRC)is one of the most commonly diagnosed cancers worldwide. Unresectable advanced, metastatic or recurrent CRC(mCRC)remains incurable for most patients. Systemic chemotherapy is standard treatment for patients with mCRC. The goals of systemic chemotherapy include prolonging survival by stopping cancer progression and palliation. In recent years, advances in the treatment of mCRC have enabled personalized care based on the tumor's molecular profile with improved outcomes for some subtypes. Targeted biologic therapies and immune checkpoint inhibitors have changed the approach to management of uncommon molecularly defined subsets of mCRC. The development of chemotherapy using cytotoxic drugs, biologic monoclonal antibodies, and immune checkpoint inhibitors has prolonged median overall survival up to approximately 30 months. In this report, we describe the evolution of systemic chemotherapy for mCRC, recent advances in standard treatment, and future prospects for the treatment of mCRC.