The AXEPT trial demonstrated that modified XELIRI (mXELIRI; capecitabine + irinotecan) was noninferior to standard treatment with FOLFIRI (fluorouracil + leucovorin + irinotecan), both ± bevacizumab, in the treatment of metastatic colorectal cancer (mCRC). The present study was designed to evaluate the cost-effectiveness of mXELIRI versus FOLFIRI as a second-line treatment of mCRC.We developed a Markov model to estimate the costs and health outcomes of mXELIRI and FOLFIRI in patients with mCRC from the Chinese payer perspective. Survival data, transition probabilities, and health utility values were obtained from published studies. The costs of drugs were obtained from the West China Hospital. Life-years (LYs), quality-adjusted life-years (QALYs) gained, incremental cost-utility ratio (ICUR), and incremental cost-effectiveness ratio (ICER) values were regarded as the primary end points. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to evaluate the impact of uncertainty of parameters in the analysis.The effectiveness was found to be 0.48 QALYs (1.14 LYs) in the mXELIRI arm and 0.41 QALYs (1.05 LYs) in the FOLFIRI arm, with total costs of 29,896.41 US dollars (USD) in the mXELIRI arm and 28,894.68 USD in the FOLFIRI arm. The ICER and ICUR with mXELIRI versus FOLFIRI were 11,130.33 USD/LY and 14,310.43 USD/QALY gained, which were less than the willingness-to-pay threshold in China (25,840.88 USD/QALY).Based on the results of this study, mXELIRI was found to be a cost-effective alternative to FOLFIRI as a second-line treatment of mCRC in patients in China.