This network meta-analysis compared the short-term and long-term efficacies of first-line chemotherapy regimens in patients with advanced colorectal cancer (CRC). The 10 regimens included folinic acid + 5-fluorouracil + oxaliplatin (FOLFOX), folinic acid + 5-fluorouracil + irinotecan (FOLFIRI), folinic acid + 5-fluorouracil + gemcitabine (FFG), folinic acid + 5-fluorouracil + trimetrexate (FFT), folinic acid + 5-fluorouracil (FF), irinotecan + oxaliplatin (IROX), raltitrexed + oxaliplatin (TOMOX), folinic acid + tegafur-uracil (FTU), raltitrexed, and capecitabine. Electronic searches were performed in the Cochrane Library, PubMed and Embase databases from inception to June 2017. Network meta-analysis combined direct and indirect evidence to obtain odds ratios (ORs) and surface under the cumulative ranking curves (SUCRA) of different chemotherapy regimens for advanced CRC. Fourteen randomized controlled trails (RCTs) covering 4,383 patients with advanced CRC were included. The results revealed that FOLFOX, FOLFIRI, IROX, and TOMOX all showed higher overall response rates (ORRs) than FF or raltitrexed. Compared with raltitrexed, the aforementioned four regimens also had higher 1-year progression-free survival (PFS) rates. In addition, FOLFOX and FOLFIRI exhibited higher disease control rates (DCRs) and 1-year PFS rates than FF or raltitrexed. Cluster analysis revealed that FOLFOX, FOLFIRI, and TOMOX had better short-term and long-term efficacies. These findings suggest FOLFOX, FOLFIRI, and TOMOX are superior to other regimens for advanced CRC. These three regimens are therefore recommended for clinical treatment of advanced CRC.