Background Colon cancer is one of the leading causes of cancer-related deaths worldwide. The increased incidence of comorbid diseases in elderly patients above 70 leads to the need of less aggressive strategies to be used in the adjuvant setting of stage III colon cancer. Method Our prospective cohort study was performed in the period from April 2017 to March 2020. Seventy-five patients with newly diagnosed stage III colon cancer received adjuvant chemotherapy after surgery. Patients who either received adjuvant chemotherapy less than 3 months due to intolerability or toxicity from medications or who have more than one type of cancers or metastatic disease from the start were excluded from the study. Patients’ clinicopathological characteristics in relation to oxaliplatin- and non-oxaliplatin-based chemotherapeutic regimens were analyzed with survival assessment. Results In our study, patients above 70 had better overall survival (OS) in the non-oxaliplatin chemotherapy group (p-value = 0.032) in contrast to OS in patients under 70 which was better in the oxaliplatin group (p-value < 0.001). By comparing the OS between the two age groups, the OS was better in patients < 70 years (p-value = 0.001). Additionally, we found that the DFS in patients above 70 was better in oxaliplatin-based regimens than in the non-oxaliplatin group (p- value = 0.011) with better survival rates (81.8% vs 15.7%), and markedly high DFS in patients under 70 for oxaliplatin based regimens (p-value < 0.001), with survival rates (31.1% vs 0%). By comparing the DFS between the two age groups, the DFS was better in patients < 70 years (p- value < 0.001). The disease recurrence was in favor of the non-oxaliplatin group with significant p-value = 0.003, while mortality occurred more in the oxaliplatin group (p-value < 0.001). Conclusions The appropriate selection of a personalized strategy for treatment of stage III colon cancer plays an important role in the outcome of the disease. Our findings supported the use of oxaliplatin-based chemotherapy as a standard treatment option in the adjuvant management of stage III colon cancer patients in all age groups. The benefit of non-oxaliplatin-based chemotherapy was limited to patients above 70 which might be an effective option for elderly patients.