Background: Regorafenib has been widely used as the later-line treatment for mCRC. This study aimed to describe the treatment modalities, as well as the efficacy and safety of regorafenib in a real-world setting. Methods: We conducted a retrospective study of patients (Pts) with refractory mCRC receiving at least one cycle of regorafenib as the third or higher line treatment from August 2017 to June 2020 in China. Demographic characteristics, treatment modality and survival were collected. The primary endpoint was overall survival. Uni- and multivariate analysis were conducted by Kaplan-Miere analysis and Cox regression model. Results: A total of 768 Pts from 10 centers were screened and 621 Pts were finally enrolled with a median age of 61 (18-84) years. 376 Pts received regorafenib monotherapy and 245 Pts accepted combination therapy. With a median follow-up time of 28.4 months, the median progression-free survival (mPFS) was 4.3 months (95%CI: 3.8-5.2) and the median overall survival (mOS) was 11.6 months (95% CI: 10.5-12.6). The mOS of Pts received regorafenib monotherapy (R, n = 376), regorafenib plus PD-1 inhibitor (R+I, n = 161), regorafenib plus chemotherapy (R+C, n = 53) and regorafenib plus chemotherapy, PD-1 inhibitor (R+C+I, n = 31) were 10.0, 13.2, 13.5 and 19.3 months, respectively (p = 0.0017). While the median PFS were 3.8, 5.4, 4.6 and 4.8 months, respectively (p = 0.4944). In multivariate analysis, treatment with R+I (HR = 0.712, 95%CI 0.521-0.973; p = 0.0330) and ECOG PS (HR = 0.400, 95%CI 0.232-0,690; p = 0.0010) were the only significant factors for superior mOS. Univariate analysis in subgroups demonstrated longer OS as well as PFS in KRAS mutated or antiangiogenesis therapy naïve Pts in R+I group than those in R group. Moreover, there was a tendency of shorter OS in Pts received 80mg as the final tolerated dose in R+I group compared to 160mg, while Pts received 120mg presented comparable survival. The incidence of all grade treatment-related adverse events was higher in R+I (87.9%) vs R (66.3%) group. Conclusions: The combination of regorafenib and PD-1 inhibitor was commonly adopted as the later-line treatment in mCRC patients in real-world practice and seemed to have a prolonged overall survival than regorafenib alone. Further confirmatory studies are warranted. Clinical trial information: NCT04835324.