Papafis, after venturing shortly in Smyrna and Alexandria, established his fortuitous enterprise working as a broker in Malta, a place he later considered his second home. His legacy of philanthropic activities include the founding of orphanages and large donations directed to educational and public services and both in Malta and Greece. In Greece he is commemorated for helping in the funding of the Greek War of Independence and in financing crucial sectors of the newly formed Greek state. He was among the primary shareholders of the National Bank of Greece, donated to the University of Athens, and the Greek Orthodox Church through the Ecumenical Patriarch of Constantinople.
His most famous contribution was the establishment of an orphanage in Thessaloniki, which he originally named "The Maltese" (Greek: "Ο Μελιτεύς"), now commonly known as Papafeio (Παπάφειο) after him. The male-only orphanage was most active after the Greek Civil War, when it sheltered orphans that numbered in the thousands.
Designed by the architect Paionidis, the building of the Papafeio took 9 years to complete and is one of the most recent historical monuments of the city of Thessaloniki, representative of the city's architecture. At times of war and other crises it was temporarily utilized by the military, mostly as a hospital, as during the Balkan Wars and both World Wars.
Excluding the above periods, the orphanage is in continuous operation until now. As per Papafis' request, as stated in his will, the institution also provides training in a number of professions to help its graduates establish themselves professionally. By the same will, the institution is placed under the administration of the Greek Orthodox Archbishop of Thessaloniki.
- "Papafeio, founder". Papafeio Orphanage. Retrieved 2010-08-03.. biography of Ioannis Papafis, founder of the Papafeio orphanage (Greek)
- Papagiannopoulos, Apostolos. Monuments of Thessaloniki. Rekos.
- "Papafeio, history". Papafeio Orphanage. Retrieved 2010-08-03.. History of the Papafeio orphanage (Greek)
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