Background: Colorectal cancer (CRC) is one of the most commonly diagnosed cancer both in Mexico and worldwide, with the peak incidence in patients >65 years. The use of adjuvant chemotherapy (CT) improves the prognosis of high-risk CRC. The benefit from fluorouracil (FU)-based CT across all age groups is not questionable, but the use of oxaliplatin (Ox) is controversial. Methods: Original, retrospective, observational study. Included patients diagnosed with CRC adenocarcinoma treated at the Instituto Nacional de Cancerología México, between 2004 to 2022. Statistical analysis required: X² and t-test, Kaplan Meier, Log Rank, and Cox Regression. Statistical significance differences were assessed when p was bilaterally <0.05. Results: From 1,238 patients with localized CRC, 275 patients were included in analysis and divided into 2 groups: young (≤ 30 years) (n = 54), and older (≥ 70 years) (n = 221). Most patients were female for both groups (55%). Comorbidities were observed in 2% of young patients and 51% of older patients (p < 0.001). Stages (S) were: II (31%; 39%), and III (59%; 47%). CT was received in 70% of young and 47% of older patients (p = 0.002). Regarding CT regimens, 56% and 21% of young and older patients respectively, had oxaliplatin (p < 0.001), while 21% of young and 32% of older patients did not complete the CT (p = 0.012). Overall survival (OS) analysis was performed considering age and S. S-II median-OS was not reached (NR) for both groups, while S-III median-OS was 170 months (m) for young versus NR for older (p = 0.690). When including CT in OS analysis, patients S-II median-OS was NR for all groups (p = 0.081), while S-III median-OS was 170 m with and 19 m without CT for young versus NR with and 89 m without CT for older, respectively (p = 0.010, 95% CI 0.059-0.123). In S-III older patients, a sub-analysis was performed considering Ox: 10-year-OS was 71% versus 60% for patients treated with and without Ox respectively (p = 0.030, 95% CI 0.25-0.93). In Cox-Regression analysis for patients with clinical stage III, regimen completion (p = 0.004; HR 0.38, 95% CI 0.201-0.745) and Ox (p = 0.022; HR 0.423, 95% CI 0.203-0.881) remained as predictor factors of OS. Conclusions: There are no studies which compare the administration of CT between young and older patients or the description of these populations in Mexico. Young patients are more likely to receive CT with Ox assumingly due to the lack of comorbidities and life expectancy. The benefit of CT on OS in young patients is not in question. An increase in OS was found in older patients who received CT with Ox, but a higher percentage of treatment discontinuation secondary to toxicity. As recommended by the literature, its essential to integrate assessment in older patients to determine which patients will benefit from complete CT regimens to increase their OS, apart from their chronological age.