In this work, the photo-Fenton process with ferrioxalate induction has been applied to perform the degradation of the organic matter from a textile effluent based on a full factorial design in order to work at its optimized condition along with obtaining a low toxicity. Experimental tests based on a three-level full factorial design (FF 33) were performed, properly varying initial pH, Fe3+ ion concentration and H2O2 concentration and using COD and color removal as response variables. Additionally, 240-min UV irradiation and 150-rpm shaking speed were set at all runs. The FF 33 experimental data were statistically represented by a quadratic polynomial function validated by the ANOVA test, suggesting the individual and combinate effects of fundamental parameters on removals. In this context, an improvement on COD removal and discoloration up to 93 and 99%, respectively, was found. The best condition of 8000 mg L−1 H2O2, 170 mg L−1 Fe3+ and initial pH 2.8 was applied to assess the toxicity effect. An extending on experiment time of about 120 min was suggested by Artemia salina-based bioassays to get a lower toxicity in environmental safety context. Finally, the photo-Fenton process with ferrioxalate induction was verified to favor and improve the pollutant degradation with higher COD removals, faster reaction kinetics and a greater availability of iron ions in comparison with the conventional photo-Fenton reaction. Besides, treated effluent with evident reduction in toxicity could be disposed without affecting the water body quality.