BACKGROUND: Metastatic colorectal cancer (mCRC) is associated with poor prognosis and limited options for later-line treatment. Regorafenib and TAS-102 have shown significant benefit and are recommended as later-line treatment for mCRC. This study aimed to investigate the progression-free survival (PFS) and overall survival (OS) of patients with mCRC treated with TAS-102 sequentially after regorafenib progression. METHODS: This population-based cohort study retrospectively collected data of 30 patients with mCRC treated with TAS-102 sequentially after regorafenib at the Harbin Medical University Cancer Hospital and the Cancer Hospital Affiliated to Shanxi Medical University from January 1, 2020, to October 1, 2023. PFS and OS were considered to be the endpoints of this study. Kaplan-Meier analysis, log-rank test, and Cox proportional hazards regression analysis were used to analyze the OS, PFS, and risk factors. RESULTS: Among the 30 patients included in the study, the median PFS (mPFS) for all patients was 3.83 months [95% confidence interval (CI): 3.09-5.59]. OS was divided into two categories: OS CONCLUSIONS: Our study demonstrated that the availability of sequential treatment options including regorafenib followed by TAS-102 prolongs the OS of patients compared to conventional monotherapy approaches. During the sequential treatment, regorafenib or TAS-102 combined with other therapeutic agents did not significantly differ from monotherapy, further investigation is required through large-scale trials.