Iron deficiency anemia continues to be a major nutritional challenge worldwide and is mainly caused by dependence on staple foods which are low in iron bioavailability. In many parts of the world, the common bean (Phaseolus vulgaris) is an important source of iron. Bean iron has very low bioavailability and household/industrial processing technologies have been shown to improve iron bioavailability. In this study, iron bioavailability of 16 Ugandan bean varieties was determined using an in vitro digestion/Caco-2 cell culture model and modeled with respect to key influencing factors; phytate, polyphenol, ferritin and iron content. The effect of extrusion cooking on iron bioavailability was also established. Iron bioavailability of white seed coat bean varieties was significantly higher than in colored seed coat varieties. A reverse trend was observed in which colored varieties showed higher polyphenol content than white ones. These results indicated that iron bioavailability can be indirectly screened for by seed coat color. Regression modeling showed that only iron and polyphenol content significantly influence iron bioavailability in beans. The linear effects of polyphenol and iron decreased iron bioavailability while their interaction increased it. Extrusion cooking process variables; raw material moisture content, extruder die temperature and feed flow rate were optimized with respect to bean iron bioavailability, paste viscosity and consumer acceptability of extruded flours. Extrusion cooking increased both iron content and iron bioavailability and gave consumer acceptable flours with reduced paste viscosity. The increase in iron content indicates possible contamination from extruder parts and may partly account for the increase in bioavailability. The optimal combination of extrusion variables was 15% moisture content, 120 C die temperature and 3 kg/h feed flow rate. Model validation experiments revealed that most of the responses could be reliably predicted, save for iron bioavailability.