Background: Regorafenib and trifluridine/tipiracil (TAS-102) are standard of care (SoC) systemic anticancer treatments (SACT) for metastatic colorectal cancer (mCRC) patients perviously treated with fluoropyrimidine (5-FU), irinotecan, & oxaliplatin-based chemotherapy. However, evidence is limited on post-chemotherapy & later SACT for patients with mCRC that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). This study assessed real-world patient characteristics and treatment patterns in community oncology practices among previously treated, not MSI-H/dMMR mCRC patients. Methods: This retrospective cohort study utilized The US Oncology Network (iKnowMed) electronic health record database, supplemented by chart review. The study cohort comprised adult, not MSI-H/dMMR mCRC patients treated with chemotherapy (5-FU/capecitabine, irinotecan, and oxaliplatin) who initiated subsequent SACT or received best supportive care (BSC) between 1/1/2016 & 12/31/2021. Index date for SACT users was the regimen start date. For patients on BSC and no subsequent SACT/BSC, index date was last chemotherapy administration date. Patients were followed from index date through 8/31/2022, date of death or last contact date, whichever occurred first. Descriptive statistics were used to report patient and treatment characteristics. Results: The study consisted of 292 mCRC patients, with a median age of 57 (range: 49, 68) years. The predominant histology was adenocarcinoma (n = 237, 81.2%) with 1.7% other histology and rest missing, 198 (67.8%) patients had Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 and 206 (70.5%) had primary tumors located in the colon. Liver (n = 207, 70.9%) and lung (n = 78, 26.7%) were the most common metastasis sites. Diabetes (n = 33, 11.3%) and peripheral vascular disease (n = 18, 6.2%) were the most common comorbidities. Eighty-seven (29.8%) patients received at least one chemotherapy in the adjuvant/neo-adjuvant setting, while majority (70.2%) patients received chemotherapies in the metastatic setting. Overall, 203 (69.5%) received SACT post-chemotherapy, 84 (28.8%) received BSC and 5 (1.7%) did not receive SACT/BSC. Among the SACT post-chemotherapy users, 30 (14.8%) received regorafenib, 25 (12.3%) received TAS-102 and 148 (72.9%) received other SACT. Other SACT included irinotecan-based (n = 76, 37.4%), oxaliplatin-based (n = 30, 14.8%), irinotecan and oxaliplatin-based (n = 6, 3.0%) chemotherapy, and anti-EGFR (n = 15, 7.4%) or anti-VEGF (n = 8, 3.0%) targeted therapies. Conclusions: Overall, only 27.1% of previously treated mCRC patients with tumors that were not MSI-H or dMMR received SoC. The real-world variability in choice of treatments and the high percentage of patients rechallenged with chemotherapy in subsequent lines, highlights an unmet need in this population.