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Three demonstrators were killed and around 50 wounded in clashes with security forces near the key southern port of Umm Qasr, the Iraqi Human Rights Commission reported.
An AFP correspondent said security forces had fired live rounds at protesters trying to block access to the port.
Two killed and 38 wounded in Baghdad protests: security sources
Since October 1, Iraq's capital and majority-Shiite south have been swept by mass demonstrations over corruption, lack of jobs and poor services that have escalated into calls for an overhaul of the ruling system.
Top leaders have publicly acknowledged the demands as legitimate and promised measures to appease protesters, including hiring drives, electoral reform and a cabinet reshuffle.
But the rallies have continued, waning on some days but swelling when demonstrators felt politicians were stalling.
On Sunday, protesters in the southern city of Nasiriyah blockaded five main bridges, shut down schools and burned tyres outside public offices in anger.
They blocked access to oil fields and companies around the city, torching as well its Shiite endowment centre, a government body that manages religious sites.
Medical sources said overnight three protesters had been shot dead and at least 47 others wounded by security forces in the city, some 300 kilometres (200 miles) south of the capital Baghdad.
An estimated 350 people have been killed and thousands wounded since October 1, according to a tally compiled by AFP as authorities are not providing precise or updated figures.
That makes the protests Iraq's deadliest grassroots movement in decades, but also its most widespread.
The rural and tribalistic south has carried the torch of the movement for weeks, with students and teachers leading rallies outside schools and public offices.
In an attempt to resume classes, the education ministry issued a directive for schools to open normally on Sunday, the first day of the work week in Iraq.
But protesters in Nasiriyah defied the order and shut down schools anyway, AFP's correspondent said.
In the oil-rich southern city of Basra, demonstrators blocked main roads just before dawn, including those leading to the ports of Umm Qasr and Khor al-Zubair.
The ports, which bring in food and medicine to Iraq but also export fuel products, have seen some delays in loading and offloading due to the unrest in recent weeks.
Clashes also pitted protesters against security forces overnight in Karbala, one of Iraq's two Shiite holy cities.
The two sides lobbed Molotov cocktails at each other from behind barricades set up in small alleyways.
"They're throwing Molotov cocktails at us and at midnight, they started shooting live rounds," one demonstrator said.
The streets were lit only by fires from the exploding makeshift grenades and green laser pointers used by demonstrators to disrupt the riot police's vision.
"Our demands are clear: the downfall of this corrupt government," said another demonstrator, his face wrapped in a black scarf.
Iraq is the 12th most corrupt country in the world, says Transparency International, and many protesters say the current political class is to blame.
They accuse elites of awarding public sector jobs based on bribes, nepotism or sectarianism, leading to an unemployment rate of 25 per cent.
Iraq's cabinet is currently discussing the 2020 budget before it is submitted to parliament and government sources say it is expected to be one of the country's largest yet.
Iraqis seal bridges, roads as protests pick up pace
Sunday's violence came a day after the surprise visit of United States Vice President Mike Pence to Iraq, where he dropped in on American troops stationed in the country's west and met top leaders in the Kurdish region in the north.
He did not, however, meet officials in Baghdad for "security reasons".
The US and Iraq have been close allies since the former led the 2003 invasion that toppled ex-dictator Saddam Hussein, but ties are now at their "coldest", officials from both countries have told AFP.
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