This study explores a comprehensive study on the effective parameters in As(III) oxidation process with the high initial concentration of 5 mg/L by using of H2O2, O3, and Cl2 oxidants. For this purpose, As(III) oxidation process was successfully optimized using a Box-Behnken design with response surface methodology (RSM). A three -level-four-variable design was applied with three numerical factors including oxidant dosing (1, 2 and 3 times the stoichiometric molar ratio), pH (6, 7 and 8), time (1, 5 and 10 min), and oxidant type (H2O2, O3, and Cl2). Oxidation results showed the highest percentage of As(III) oxidation at zero levels of oxidant dosing, pH, and time variables were achieved by Cl2 oxidant compared to O3 and H2O2 oxidants. According to factors F-values, time, oxidant type, and oxidant dosing factors are the most effective factors on As(III) oxidation efficiency, respectively and pH factor and its interactions indicated the slight effects. The optimal oxidation conditions were oxidant dosing of 1.89 ratio, pH= 7.75, t=4.06 min by Cl2 oxidant causing complete As(III) oxidation. Finally, validation of the proposed optimal conditions for As(III) oxidation was investigated by conducting the oxidation process under the optimal conditions with real well water sample with a specific As(III) concentration of 5 mg/L, yielding an oxidation efficiency of 99.8% and 99.5%, respectively. The findings provide new insight into superior efficiency of Cl2 compared to H2O2 and O3 oxidants in oxidation of As(III) as an effective approach to solve the low removal efficiency problem of As(III).